Study targets overlooked barrier in pancreatic cancer
Researchers at McGovern Medical School at UTHealth Houston are collaborating on a National Institutes of Health-funded study investigating whether a protein best known for its role in blood clotting could help explain why pancreatic cancer is so resistant to immunotherapy.
Faraz Bishehsari, MD, PhD, professor, founding director of the Gastroenterology Research Center, and Atilla Ertan, MD, Chair in Gastroenterology Research at McGovern Medical School, is collaborating with Taslim Al-Hilal, PhD, associate professor of molecular pharmaceutics at the University of Utah, and Paul Grippo, PhD, associate professor of gastroenterology and hepatology at the University of Chicago, on the newly funded $3.1 million R01 project from the National Cancer Institute.
The research focuses on pancreatic ductal adenocarcinoma, or PDAC, and the role of fibrin within the tumor environment. While fibrin normally plays an important role in blood clotting, emerging research suggests that its accumulation within pancreatic tumors may also contribute to an environment that protects cancer cells from the body’s immune response.
Pancreatic cancer has proven particularly difficult to treat with immunotherapy. PDAC tumors contain dense, scar-like tissue known as stroma and have relatively few of the immune cells and signaling molecules needed for an effective antitumor response. Previous efforts to improve treatment by reducing the amount of stroma have not produced the hoped-for results, prompting researchers to look more closely at the individual components within it.
“Instead of focusing on the amount of stroma, we are looking at whether specific components within it may be driving immune suppression,” Bishehsari said. “Our collaborative study will investigate whether fibrin acts as a key architect of an immune-resistant tumor environment.”
Preliminary findings suggest that as cross-linked fibrin accumulates within pancreatic tumors, it may increase the stiffness of the surrounding tissue and affect the behavior of macrophages, immune cells that can either help fight disease or, within tumors, be reprogrammed in ways that support cancer growth. The researchers will examine whether those changes also interfere with the activity of cancer-fighting T cells.
The team will investigate how features of the tumor microenvironment contribute to immune suppression and cancer progression, while testing new strategies designed to restore antitumor immune activity.
“The ultimate goal is to determine whether targeting fibrin-related pathways can transform pancreatic cancer from an immunologically ‘cold’ tumor, largely invisible to the immune system, into one that is more responsive to modern immunotherapies,” Bishehsari said.
The findings could ultimately point researchers toward a new way of making pancreatic tumors more vulnerable to the body’s immune response.